Kukoamine B, an amide alkaloid, protects against NMDA-induced neurotoxicity and potential mechanisms in vitro

Xiao-Long Hu, Li-Ping Guo, Qi Song, Qiao Zhang, Ying Chen, Jian Wang, Wei-Hong Meng, Qing-Chun Zhao  

Abstract

A major cause of cerebral ischemia is overactivation of the N-methyl-D-aspartate receptors (NMDARs). Therefore, NMDAR antagonists are needed for the treatment of cerebral ischemia. In our research, KuB protected the SH-SY5Y cells against NMDA-induced injury,apoptosis, LDH release and MMP loss. In addition, KuB could decrease MDA levels while increasing SOD activity. Meanwhile, KuB decreased NADPH oxidase-mediated ROSproduction, inhibited Ca2+ influx, and increased the Bcl-2/Bax ratio. Furthermore, KuB not only down-regulated expression of the NR2B subunit of NMDAR but also actively modulated expression of the signaling molecules downstream of NR2B, including p-ERK, p-CREB, p-AKT and SAPKs. Finally, docking results showed that KuB had a high affinity for NR2B-containing NMDARs. Therefore, we conclude that KuB protected the SH-SY5Y cells from NMDA-induced injury likely by antagonizing NMDARs and reducing oxidative stress.

 Kukoamine B (>98%) was purchased from Chengdu Biopurify Phytochemicals Ltd. (China).